Valproic acid, salts thereof, amides thereof, and derivatives thereof are available for treating epilepsy. For example, sodium valproate is useful for treating epileptic phenomena. This drug is effective for its intended therapy, however, there are shortcomings associated with this drug. For instance, sodium valproate is hygroscopic and liquifies very rapidly. Additionally, the drug exhibits a short-half life that can lead to fluctuations in blood antiepileptic drug levels. These properties can interfere with the manufacture and release of the drug from a dosage form, and are drawbacks in the management of epilepsies and other disorders which may be treated with sodium valproate.
A relationship has been reported between epilepsy, affective illness and migraine. Although the three disorders are distinct, they all are paroxysmal dysregulations of the nervous system that partially overlap in their pharmacology. Valproic acid and its pharmaceutically acceptable salts have been found to be effective in treating all three syndromes, suggesting the presence of shared underlying pathophysiology.
Although valproic acid and its pharmaceutically acceptable salts have been shown to be effective in both the treatment and prevention of migraine, its mechanism of anti-migraine action is unclear. It is, however, believed that valproic acid increases brain gamma-aminobutyric acid (GABA) levels and in doing so may activate the GABA receptor and suppresses migraine-related events.
It will be appreciated by those skilled in the art that controlled or sustained release compositions employing a valproic acid, pharmaceutically acceptable salt thereof, amide thereof, or derivative thereof would be particularly useful in the treatment and prevention of migraine or for the treatment of those in clinical need of antiepileptic therapy.